The cerebral cortex is thought to be the seat of the complex processes involved in high-level cognition, perception and movement. Of the many cortical areas, the function of the primary visual cortex, or V1, is perhaps the best understood: Many of the transformations that V1 performs on the representation of the retinal image have been described in great detail;the anatomy of the connections within V1 and from its inputs have been well described;synaptic integration in single neurons has been studied with intracellular recording. As a result, it has been possible to construct detailed and realistic models of the function of V1. We have focused in this project on understanding the principles of cortical processing, by trying to provide experimental tests of the different models and by developing a more detailed description of synaptic integration in cortical neurons. In the current period, we will focus on those aspects of neuronal behavior that deviate from the simplest linear model of cortical function and try to understand the sources of these nonlinearities. The first aim is related to contrast-normalization (or more generally, stimulus-based normalization), which is thought to underlie perceptual constancy. Contrast-invariant orientation tuning is one aspect of normalization and our current understanding is that it might arise from the interaction of response variability and threshold. We seek to understand the source and properties of this variability. The second aim focuses on contrast-dependent changes in the tuning and response timing of neurons. The most successful model of these properties has relied on inhibitory inputs to neurons, but is not well supported by experimental evidence. We therefore seek mechanisms related to threshold, synaptic depression and other nonlinearities in the visual pathways. In the third aim, we propose to study nonlinearities in complex cells, using a recently developed measure of the computation that these cells use to integrate their visual inputs. We will test models of how cells of different cells perform this computation. We hope that the resulting data will contribute to a more coherent understanding of cortical function. PUBLIC HEALTH RELEVANCE: We are studying the fundamental neural mechanisms by which the cerebral cortex processes visual information. From these experiments we hope to gain an understanding not only of how the visual system works, but also of how the brain performs other higher perceptual and cognitive functions. Understanding these processes in the normal brain may ultimately help us to understand how they malfunction in disease states, including epilepsy and mental disorders. Understanding the mechanisms of visual processing are also critical to constructing effective prosthetic and rehabilitative aids to vision.